Vaccines to protect against infectious diseases have been used to improve human and animal health. One successful technology for viral vaccines is to immunize animals or humans with a weakened or attenuated strain of the virus (a “live, attenuated virus”). Due to limited replication after immunization, the attenuated strain does not cause disease. However, the limited viral replication is sufficient to express the full repertoire of viral antigens and generates potent and long-lasting immune responses to the virus. Thus, upon subsequent exposure to a pathogenic strain of the virus, the immunized individual is protected from disease.
Recent technical advances, such as reassortment, reverse genetics and cold adaptation, have led to advances of live, attenuated viruses for influenza and rotavirus. A number of live, viral vaccines developed with recombinant DNA technologies are in human clinical testing, including vaccines for West Nile disease, dengue fever, malaria, tuberculosis and HIV. These recombinant viral vaccines rely on manipulation of well-characterized attenuated viral vaccines, such as adenovirus, vaccinia virus, yellow fever 17D or the dengue virus, DEN-2 PDK-53. As a group, live attenuated viral vaccines are amongst the most successful medical interventions in human history, second only to the advent of antibiotics and hold the promise to improve public health throughout the world.
Other vaccines have been developed by inactivating viruses after growth in cell culture. These “killed virus” vaccines induce immune responses due to the presence of high concentrations of antigen present. Examples of effective killed viral vaccines include, but are not limited to, vaccine for rabies, influenza, hepatitis A, and poliovirus.
Flaviviruses cause a number of human and animal diseases of significant impact. They are enveloped viruses with a RNA genome of approximately 11,000 bases. Most of the flaviviruses are transmitted by an arthropod vector, commonly mosquitoes. There are over 70 different flaviviruses that are grouped into three major categories based on serology: the dengue group, the Japanese encephalitis group and the yellow fever group. Expanding urbanization, worldwide travel and environmental changes (such as deforestation or rain patterns) have lead to the emergence of several flaviviruses as threats to human public health. Such viruses include, but are not limited to, yellow fever virus, the dengue viruses, West Nile virus, Japanese encephalitis virus, and tick-borne encephalitis viruses.
Both live, attenuated viral vaccines and killed virus vaccines have been developed that are safe and protect against flavivirus diseases, for example, yellow fever and Japanese encephalitis.